CD8 memory T cells: cross-reactivity and heterologous immunity

Virus-specific memory T cell populations demonstrate plasticity in antigen recognition and in their ability to accommodate new memory T cell populations. The degeneracy of T cell antigen recognition and the flexibility of diverse antigen-specific repertoires allow the host to respond to a multitude of pathogens while accommodating these numerous large memory pools in a finite immune system. These cross-reactive memory T cells can be employed in immune responses and mediate protective immunity, but they can also induce life-threatening immunopathology or impede transplantation tolerance and graft survival. Here we discuss examples of altered viral pathogenesis occurring as a consequence of heterologous T cell immunity and propose models for the maintenance of a dynamic pool of memory cells.     

Albendazole is Not Effective for Primary Treatment of Hepatic Hydatid Cysts

Introduction In current practice, minimal invazive interventions such as percutaneous drainage and laparoscopic surgery in adjunct treatment with benzimidazoles have been gaining acceptance in treatment of hydatid cystic disease with minimal morbidity and mortality. In this prospective study, the efficacy and validity of primary medical therapy in the treatment of hydatid cystic disease has been investigated. Patients and methods Sixty-five patients with hepatic cystic disease were treated with albendazole alone between January 2004 and June 2007. All of the patients were administrated albendazole as 10 mg kg⁻¹ day⁻¹ divided into two equal doses for 6 months with ultrasonography (USG), serological tests, full-blood cell count and hepatic function tests performed in 2 months intervals in the course of treatment. Results Fifty of the patients were female and 15 were male with a mean age of 47.0 ± 16.9 (17–80). A total number of 106 cysts were present in 65 patients. Mean cystic diameter was 5.5 ± 3.6 (1–16). In 41 of the patients, cysts were solitary and in remaining 24 patients cysts were multiple. Mean follow-up period was 28.3 ± 8.6 (12–42) months. The overall success rate of albendazole therapy was 18 % (12/65) in the study. Conclusion Albendazole therapy for hepatic hydatidosis is not effective in the vast majority of patients and, therefore, should not be used as the primary therapy for patients who are surgical candidates.     

Microvessel density and vascular endothelial growth factor expression as predictors of childrens’ survival from cerebellar medulloblastoma

Cerebellar medulloblastoma is the most common malignant brain tumor of childhood. This neoplasm is highly vascular and has a high growth rate. We aimed to determine whether high microvessel density (MVD) and expression of vascular endothelial growth factor (VEGF) in medulloblastoma tissue is correlated with survival time in children with this tumor. Tissue from 32 cerebellar medulloblastomas in 14 girls and 18 boys was studied. The standard-risk group comprised patients older than 3 years, without metastases of medulloblastoma and a residual post-operative tumor with a surface area less than 1.5 cm². The patients assigned to a high-risk group had at least one of the following indicators: younger than 3 years, metastases, or a residual post-operative tumor with a surface area larger than 1.5 cm². For each tumor, MVD was determined and the expression of VEGF was assessed using immunohistochemical techniques. The 5-year survival rate for the 32 patients was 56.2%. Five-year survival rates were 70.6% and 40.0% for patients in the standard-risk and high-risk groups, respectively. The mean (±standard deviation, SD) MVD for all patients was 22.0 ± 9.1 microvessels per 0.7 mm². There was no difference in the survival rate between the groups with above-average MVD and below-average MVD (66.7% and 50.0%, respectively). Testing revealed 7 tumors with VEGF expression and 25 without. The 5-year survival rates for these 2 groups were not significantly different (57.1% vs. 56.0%, respectively). The mean (±SD) MVD values for the VEGF-positive and VEGF-negative groups were not significantly different (19.1 ± 6.5 vs. 22.9 ± 9.7 microvessels per 0.7 mm², respectively, Mann–Whitney U-test = 78.5, Z = ?0.41, p = 0.68). There were no significant correlations between risk groups and expression of VEGF or MVD. These results indicate that neither high MVD nor the expression of VEGF in tumor tissue predicts poor prognosis in children with cerebellar medulloblastoma.     

Extended lymphadenectomy in stomach cancer]

The results of surgical treatment in 120 patients with cancer of the stomach have been analyzed. Metastatic involvement in all groups of lymphatic nodes was revealed in 68.3% cases, retroperitoneal metastases were detected in 46 patients (38.3%). 38 subtotal resections of the stomach and 82 gastrectomies with retroperitoneal lymphadenectomy R2 and R3 were performed. Esophagojejunoanastomosis end-to-end with a loop excluded by Roux was applied in 110 patients and esophagoduodenoanastomosis--in 10 patients. Insufficiency of esophagointestinal anastomosis was revealed in 3 patients. The rate of complications was 29.2%, lethality--8.3%. High rate of postoperative complications and lethality were explained by initially severe conditions of the patients (61%) and by complicated forms of gastric cancer in 6 patients. Improvement of early results of surgical interventions lies in the usage of antibacterial prophylaxis, preventive intravenous introductions of 5-fluorouracil, adequate drainage of the abdominal cavity, careful preparation and ligation in the course of the operation.     

DYSPLASIA AND DISORDER OF CELL MEMBRANE ENTIRETY IN IRON-DEFICIENCY ANEMIA

Peripheral blood smears of 43 patients (26 males, median age 18 months, range: 6–180 months) with nutritional iron-deficiency anemia (IDA) were examined for the presence of trilineage hematological dysplasia. Twelve patients were reexamined for dysplastic findings after achieving a normal Hb and hematocrit level for age by the end of 2–3 months of iron treatment. A control group of 17 age-matched healthy children were also included. Neutrophils with loss of membrane entirety and protrusions were remarkable in 34/43 (79%) in the IDA group versus 1/12 (8%) after iron treatment and none of the control group. Microspherocytes were seen in 9/43 (21%) of IDA patients. Additionally, trilienage dysplasia was observed in the bone marrow samples available in 3 of the patients. It has been shown that iron-deficiency results in cellular DNA and RNA alterations, cell-cycle G1/S phase arrest, and apoptosis. Rac GTPases have been shown to control actin cytoskeleton, influencing cell polarity, microtubule dynamics, and the cytoskeletal organization of hematopoietic cells. Thus, the findings described above in neutrophils and red cells suggest a plausible link between iron and the Rac GTPase gene family. It may be a new avenue for iron waiting for proof.     

Private specificities of CD8 T cell responses control patterns of heterologous immunity

CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Ralpha by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.